Crohn's disease (CD) is principally characterized by chronic and recurrent inflammation of the gastrointestinal tract, most commonly found in the ileo-colonic region. The chronicity and severity of intestinal inflammation together contribute to progressive, cumulative, deep, transmural intestinal damage, including stricturing, obstruction, abscesses, and fistulae. Both intestinal inflammation and its chronic complications result in a range of symptoms subsequently leading to patient presentations with diarrhea, abdominal pain, and anemia related to intestinal blood loss. Measuring disease activity and severity are essential for decision of treatment intensity early in the disease course and longitudinal monitoring of therapeutic efficacy. This review will summarize the transition from subjective symptoms driving disease activity indices, into increasingly objective and quantitative measures of intestinal injury by direct mucosal assessment (endoscopy), cross-sectional imaging, and surrogate biomarkers. Specific commentary on intestinal stricture and perianal fistula assessment and management are presented in accompanying sections of this series.